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Review
. 2019 Apr 15:11:1758835919836374.
doi: 10.1177/1758835919836374. eCollection 2019.

First-line afatinib for the treatment of EGFR mutation-positive non-small-cell lung cancer in the 'real-world' clinical setting

Keunchil Park  1 , Darren Wan-Teck Lim  2 , Isamu Okamoto  3 , James Chih-Hsin Yang  4
Affiliations
Review

First-line afatinib for the treatment of EGFR mutation-positive non-small-cell lung cancer in the 'real-world' clinical setting

Keunchil Park et al. Ther Adv Med Oncol. .

Abstract

Afatinib is an ErbB family blocker that is approved for the treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Pivotal randomized clinical studies demonstrated that afatinib significantly prolonged progression-free survival compared with platinum-based chemotherapy (LUX-Lung 3, LUX-Lung 6), and with gefitinib (LUX-Lung 7), with manageable side effects. However, these results were derived from controlled studies conducted in selected patients and are not necessarily representative of real-world use of afatinib. To gain a broader understanding of the effectiveness and safety of first-line afatinib, we have undertaken a literature review of real-world studies that have assessed its use in a variety of patient populations. We focused on patients with uncommon EGFR mutations, brain metastases, or those of advanced age, as these patients are often excluded from clinical studies but are regularly seen in routine clinical practice. The available real-world studies suggest that afatinib has clinical activity, and is tolerable, in diverse patient populations in an everyday clinical practice setting. Moreover, consistent with LUX-Lung 7, several real-world comparative studies indicate that afatinib might confer better efficacy than first-generation EGFR tyrosine kinase inhibitors. Tolerability-guided dose adjustment, undertaken in 21-68% of patients in clinical practice, did not appear to reduce the efficacy of afatinib. Taken together, these findings provide further support for the use of afatinib as a treatment option in patients with EGFR mutation-positive NSCLC.

Keywords: EGFR tyrosine kinase inhibitors; NSCLC; afatinib; brain metastases; real-world; uncommon mutations.

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Conflict of interest statement

Conflict of interest statement: KP has received personal fees from Boehringer Ingelheim, Clovis, Eli Lilly, Hanmi, Kyowa Hakko Kirin, Ono, Novartis, and Roche; and research funding from AstraZeneca. IO has received honoraria from Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceuticals, Ono Pharmaceuticals, Merck Sharpe and Dohme, Lilly, Bristol-Myers Squibb, Chugai Pharma; and research funding from Boehringer Ingelheim. JY has received personal fees from Boehringer Ingelheim, AstraZeneca, Roche, Chugai, Eli Lilly, Clovis, Pfizer, Novartis, Merck Sharpe and Dohme, Astellas, Bayer, Innopharma, and Celgene; and research grants from Boehringer Ingelheim and AstraZeneca. DL reports no conflicts of interest.

Figures

Figure 1.
Figure 1.
Progression-free survival in patients receiving gefitinib, erlotinib, or afatinib in a real-world study of 448 patients with EGFR mutation-positive (L858R or del19) non-small-cell lung cancer (NSCLC). (Reproduced with permission from Kuan et al.; https://creativecommons.org/licenses/by/3.0/.)
Figure 2.
Figure 2.
Progression-free survival following first-line afatinib, gefitinib, or erlotinib in 467 patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). (Reproduced with permission from Kim et al.)
Figure 3.
Figure 3.
Progression-free survival in patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received first-line afatinib at doses of 30 mg or 40 mg. (Reproduced with permission from Tu et al.; https://creativecommons.org/licenses/by/3.0/.)
See this image and copyright information in PMC

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